Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H23NO.ClH |
Molecular Weight | 305.842 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN(C)CCOC(C1=CC=CC=C1)C2=C(C)C=CC=C2
InChI
InChIKey=UQZKYYIKWZOKKD-UHFFFAOYSA-N
InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C18H23NO |
Molecular Weight | 269.3813 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdfCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499 |
97.7 µM [IC50] | ||
Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9464369 |
6.0 µM [Ki] | ||
Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date-3.99081603E11 |
|||
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date-3.99081603E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41.89 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
49.19 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1739.15 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1772.44 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.02 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
22.29 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7% |
ORPHENADRINE plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg 1 times / day steady, oral Highest studied dose Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: depression Age Group: adult Sources: |
|
2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Toxic reaction (NOS) | grade 5 | 2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
partial | ||||
partial | ||||
partial | ||||
partial | ||||
strong | ||||
strong | ||||
strong | ||||
weak [IC50 65 uM] | ||||
weak [IC50 >100 uM] | ||||
weak [IC50 >100 uM] | ||||
yes [IC50 2.5 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/12813002/ |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Prochlorperazine in childhood: side-effects. | 1977 |
|
Reversal of orphenadrine-induced ventricular tachycardia with physostigmine. | 1991 Nov-Dec |
|
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia. | 2003 Dec 15 |
|
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. | 2003 Jan 1 |
|
Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine. | 2003 Jun |
|
Upregulation of cytochromes P450 2B in rat liver by orphenadrine. | 2003 Jun |
|
Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats. | 2003 Nov |
|
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. | 2003 Nov 17 |
|
300-Hz subthalamic oscillations in Parkinson's disease. | 2003 Oct |
|
[Diclofenac 75mg. and 30 mg. orfenadine (Neodolpasse) versus placebo and piroxicam in postoperative analgesia after arthroscopy]. | 2004 |
|
Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. | 2004 Aug |
|
Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338. | 2004 Aug 23 |
|
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. | 2004 Jan 12 |
|
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer. | 2004 Jan 12 |
|
Objective high-frequency tinnitus of middle-ear myoclonus. | 2004 Mar |
|
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.]. | 2005 Apr |
|
Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study. | 2005 Aug 22 |
|
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A. | 2005 Feb 27 |
|
Dimemorfan N-demethylation by mouse liver microsomal cytochrome P450 enzymes. | 2005 Jul 1 |
|
Catanionic mixtures involving a drug: a rather general concept that can be utilized for prolonged drug release from gels. | 2006 Apr |
|
Pharmacokinetic study of orphenadrine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). | 2006 Jul 24 |
|
Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine. | 2006 May |
|
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer. | 2006 May 24 |
|
Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study. | 2006 May 8 |
|
Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction. | 2006 Sep |
|
Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient. | 2007 |
|
Evaluation of enantioselective binding of basic drugs to plasma by ACE. | 2007 Aug |
|
Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE. | 2007 Aug |
|
Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656. | 2007 Dec |
|
[Enzyme kinetics of schizandrin metabolism and sex differences in rat liver microsomes]. | 2007 Jul |
|
Determination of paracetamol and orphenadrine citrate in pharmaceutical tablets by modeling of spectrophotometric data using partial least-squares and artificial neural networks. | 2007 Oct |
|
Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition. | 2008 Aug |
|
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU. | 2008 Jan |
|
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. | 2008 May |
|
The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine. | 2009 Aug |
|
Fixed drug eruption resulting from fluconazole use: a case report. | 2009 Jul 6 |
|
Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice. | 2009 Jul-Aug |
|
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. | 2009 Jun 3 |
|
Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
|
Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541. | 2010 |
|
Testosterone hydroxylation in bovine liver: enzyme kinetic and inhibition study. | 2010 Apr |
|
Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search. | 2010 Apr 15 |
|
Orphenadrinium picrate. | 2010 Dec 18 |
|
Orphenadrinium picrate picric acid. | 2010 Feb 24 |
|
(2-Methyl-phen-yl)(phen-yl)methanol. | 2010 Jul 31 |
|
Pharmacologic management of chronic pain. | 2010 Jun |
|
7-Benzyloxyresorufin-O-dealkylase activity as a marker for measuring cytochrome P450 CYP3A induction in mouse liver. | 2010 Mar 1 |
|
Opiate sparing effect of fixed combination of diclophenac and orphenadrine after unilateral total hip arthroplasty: A double-blind, randomized, placebo-controlled, multi-centre clinical trial. | 2010 Nov |
|
Full recovery from a potentially lethal dose of orphenadrine ingestion using conservative treatment: a case report. | 2010 Nov |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
Patents
Sample Use Guides
Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours.
Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Jul 05 23:52:24 UTC 2023
by
admin
on
Wed Jul 05 23:52:24 UTC 2023
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Record UNII |
UBY910DUXH
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Record Status |
Validated (UNII)
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Record Version |
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WHO-VATC |
QN04AB02
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WHO-ATC |
N04AB02
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NCI_THESAURUS |
C29704
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C78075
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202723
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DTXSID5025815
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82357
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UBY910DUXH
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DBSALT001021
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9568
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60902
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341-69-5
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100000085503
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SUB03547MIG
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206-435-4
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CHEMBL900
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Orphenadrine hydrochloride
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ACTIVE MOIETY |